About

Professor Rosa Uribe's research centers on the development and genetic regulation of the enteric nervous system, particularly using zebrafish as a model organism. Her work extensively explores the molecular and cellular mechanisms underlying neural crest cell migration, differentiation, and colonization of the gut. She has contributed significant insights into the role of signaling pathways such as BMP and Retinoic Acid, as well as transcription factors like Meis3, in orchestrating the development of the enteric nervous system. Professor Uribe's lab employs advanced techniques including single-cell transcriptomics and CRISPR-Cas9 mediated gene screening to map neural crest lineages and identify genes critical for enteric nervous system formation. Her research also extends to the epigenetic regulation of developmental processes, exemplified by studies on histone demethylase KDM4B and its role in otic vesicle invagination. Throughout her career, Professor Uribe has collaborated on projects that elucidate the genetic and cellular basis of neural development, including investigations into retinal progenitor cell differentiation and the genetic code expansion in eukaryotes. Her contributions have advanced understanding of gene-environment interactions during vertebrate development and have provided valuable protocols and atlases for the scientific community studying neural crest biology and enteric nervous system ontogeny.

Research topics

• Genetics
• Cell biology
• Biology
• Chemistry
• Neuroscience
• Cancer research
• Molecular biology
• Biochemistry
• Anatomy
• Computational biology
• Evolutionary biology

Selected publications

• Whole‐Gut Spatial Genomic Analysis Reveals Molecular Regionalization of the Differentiating Zebrafish Enteric Nervous System

  The FASEB Journal · 2025-09-05

  articleOpen accessSenior authorCorresponding

  The enteric nervous system (ENS) is the intrinsic nervous system of the gut and controls essential functions, such as gut motility, intestinal barrier function, and water balance. The ENS displays a complex 3D architecture within the context of the gut and specific transcriptional states needed to control gut homeostasis. During development, the ENS develops from enteric neural progenitor cells (ENPs) that migrate into the gut and differentiate into functionally diverse neuron types. Incorrect ENS development can disrupt ENS function and induce various gut disorders, including the congenital disease Hirschsprung disease, or various other functional gut neurological disorders, such as esophageal achalasia. In this study, we used the zebrafish larval model and performed whole gut spatial genomic analysis (SGA) of the differentiating ENS at cellular resolution. To that end, a pipeline was developed that integrated early and late developmental ENS stages by linking various spatial and transcriptional dimensions to discover regionalized cellular groups and their co-expression similarity. We identified 3D networks of intact ENS surrounding the gut and predicted cellular connectivity properties based on the stage. Spatial variable genes, such as hoxb5b, hoxa4a, etv1, and ret, were regionalized along gut axes, suggesting they may have a precise spatiotemporal control of ENS development. The application of SGA to ENS development provides new insights into its cellular transcriptional networks and interactions and provides a baseline data set to further advance our understanding of gut neurodevelopmental disorders such as Hirschsprung disease and congenital enteric neuropathies.

  PublisherOA PDFDOI

• Whole-gut spatial genomic analysis reveals molecular regionalization of the differentiating zebrafish enteric nervous system

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-21

  preprintOpen accessSenior authorCorresponding

  Abstract The enteric nervous system (ENS) is the intrinsic nervous system of the gut and controls essential functions, such as gut motility, intestinal barrier function, and water balance. The ENS displays a complex 3D architecture within the context of the gut and specific transcriptional states needed to control gut homeostasis. During development, the ENS develops from enteric neural progenitor cells (ENPs) that migrate into the gut and differentiate into functionally diverse neuron types. Incorrect ENS development can disrupt ENS function and induce various gut disorders, including the congenital disease Hirschsprung disease, or various other functional gut neurological disorders, such as esophageal achalasia. In this study, we used the zebrafish larval model and performed whole gut spatial genomic analysis (SGA) of the differentiating ENS at cellular resolution. To that end, a pipeline was developed that integrated early and late developmental ENS stages by linking various spatial and transcriptional dimensions to discover regionalized cellular groups and their co-expression similarity. We identified 3D networks of intact ENS surrounding the gut and predicted cellular connectivity properties based on the stage. Spatial variable genes, such as hoxb5b , hoxa4a , etv1 , and ret , were regionalized along gut axes, suggesting they may have a precise spatiotemporal control of ENS development. The application of SGA to ENS development provides new insights into its cellular transcriptional networks and interactions, and provides a baseline data set to further advance our understanding of gut neurodevelopmental disorders such as Hirschsprung disease and congenital enteric neuropathies.

  PublisherOA PDFDOI

• <scp>BMP</scp> signaling pathway member expression is enriched in enteric neural progenitors and required for zebrafish enteric nervous system development

  Developmental Dynamics · 2024-09-19 · 5 citations

  articleOpen accessSenior authorCorresponding

  Abstract Background The vertebrate enteric nervous system (ENS) consists of a series of interconnected ganglia within the gastrointestinal (GI) tract, formed during development following migration of enteric neural crest cells (ENCCs) into the primitive gut tube. Much work has been done to unravel the complex nature of extrinsic and intrinsic factors that regulate processes that direct migration, proliferation, and differentiation of ENCCs. However, ENS development is a complex process, and we still have much to learn regarding the signaling factors that regulate ENCC development. Results Here in zebrafish, through transcriptomic, in situ transcript expression, immunohistochemical analysis, and chemical attenuation, we identified a time‐dependent role for bone morphogenetic protein (BMP) in the maintenance of Phox2bb + enteric progenitor numbers and/or time of differentiation of the progenitor pool. In support of our in silico transcriptomic analysis, we identified expression of a novel ENS ligand‐encoding transcript, bmp5 , within developmental regions of ENCCs. Through generation of a novel mutant bmp5 wmr2 and bmp5 crispants, we identified a functional role for BMP5 in proper GI tract colonization, whereby phox2bb + enteric progenitor numbers were reduced. Conclusion Altogether, this work identified time‐dependent roles for BMP signaling and a novel extrinsic factor, BMP5, that is necessary for vertebrate ENS formation.

  PublisherOA PDFDOI

• Genetic regulation of enteric nervous system development in zebrafish

  Biochemical Society Transactions · 2024-01-04 · 13 citations

  reviewOpen access1st authorCorresponding

  The enteric nervous system (ENS) is a complex series of interconnected neurons and glia that reside within and along the entire length of the gastrointestinal tract. ENS functions are vital to gut homeostasis and digestion, including local control of peristalsis, water balance, and intestinal cell barrier function. How the ENS develops during embryological development is a topic of great concern, as defects in ENS development can result in various diseases, the most common being Hirschsprung disease, in which variable regions of the infant gut lack ENS, with the distal colon most affected. Deciphering how the ENS forms from its progenitor cells, enteric neural crest cells, is an active area of research across various animal models. The vertebrate animal model, zebrafish, has been increasingly leveraged to understand early ENS formation, and over the past 20 years has contributed to our knowledge of the genetic regulation that underlies enteric development. In this review, I summarize our knowledge regarding the genetic regulation of zebrafish enteric neuronal development, and based on the most current literature, present a gene regulatory network inferred to underlie its construction. I also provide perspectives on areas for future zebrafish ENS research.

  PublisherOA PDFDOI

• Expansion of a neural crest gene signature following ectopic MYCN expression in sympathoadrenal lineage cells in vivo

  PLoS ONE · 2024-09-18

  articleOpen accessSenior author

  Neural crest cells (NCC) are multipotent migratory stem cells that originate from the neural tube during early vertebrate embryogenesis. NCCs give rise to a variety of cell types within the developing organism, including neurons and glia of the sympathetic nervous system. It has been suggested that failure in correct NCC differentiation leads to several diseases, including neuroblastoma (NB). During normal NCC development, MYCN is transiently expressed to promote NCC migration, and its downregulation precedes neuronal differentiation. Overexpression of MYCN has been linked to high-risk and aggressive NB progression. For this reason, understanding the effect overexpression of this oncogene has on the development of NCC-derived sympathoadrenal progenitors (SAP), which later give rise to sympathetic nerves, will help elucidate the developmental mechanisms that may prime the onset of NB. Here, we found that overexpressing human EGFP-MYCN within SAP lineage cells in zebrafish led to the transient formation of an abnormal SAP population, which displayed expanded and elevated expression of NCC markers while paradoxically also co-expressing SAP and neuronal differentiation markers. The aberrant NCC signature was corroborated with in vivo time-lapse confocal imaging in zebrafish larvae, which revealed transient expansion of sox10 reporter expression in MYCN overexpressing SAPs during the early stages of SAP development. In these aberrant MYCN overexpressing SAP cells, we also found evidence of dampened BMP signaling activity, indicating that BMP signaling disruption occurs following elevated MYCN expression. Furthermore, we discovered that pharmacological inhibition of BMP signaling was sufficient to create an aberrant NCC gene signature in SAP cells, phenocopying MYCN overexpression. Together, our results suggest that MYCN overexpression in SAPs disrupts their differentiation by eliciting abnormal NCC gene expression programs, and dampening BMP signaling response, having developmental implications for the priming of NB in vivo.

  PublisherDOI

• Expansion of a neural crest gene signature following ectopic MYCN expression in sympathoadrenal lineage cells in vivo

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-04-04

  preprintOpen accessSenior authorCorresponding

  Abstract Neural crest cells (NCC) are multipotent migratory stem cells which originate from the neural tube during early vertebrate embryogenesis. NCC give rise to a variety of cell types within the developing organism, including neurons and glia of the sympathetic nervous system. It has been suggested that failure in correct NCC differentiation leads to several diseases, including neuroblastoma (NB). During normal NCC development, MYCN is transiently expressed to promote NCC migration, and its downregulation precedes neuronal differentiation. Overexpression of MYCN has been linked to high-risk and aggressive NB progression. For this reason, understanding the effect overexpression of this oncogene has on development of NCC-derived sympathoadrenal progenitors (SAP), which later give rise to sympathetic nerves, will help elucidate the developmental mechanisms that may prime the onset of NB. Here, we found that overexpressing human EGFP-MYCN within SAP lineage cells in zebrafish led to the transient formation of an abnormal SAP population which displayed expanded and elevated expression of NCC markers, while paradoxically also co-expressing SAP and neuronal differentiation markers. The aberrant NCC signature was corroborated with in vivo time lapse confocal imaging in zebrafish larvae, which revealed transient expansion of sox10 reporter expression in MYCN overexpressing SAPs during the early stages of SAP development. In these aberrant MYCN overexpressing SAP cells, we also found evidence of dampened BMP signaling activity, indicating that BMP signaling disruption occurs following elevated MYCN expression, and suggesting BMP is functionally important for the NCC to SAP differentiation transition. In agreement, we discovered that pharmacological inhibition of BMP signaling was sufficient to create an aberrant NCC gene signature in SAP cells, phenocopying MYCN overexpression. Together, our results suggest that MYCN overexpression in SAPs disrupts their differentiation by eliciting abnormal NCC gene expression programs, and dampening BMP signaling response, having developmental implications for the priming of NB in vivo .

  PublisherOA PDFDOI

• Fibroblast Growth Factor (FGF) 13

  Differentiation · 2024-09-25 · 3 citations

  reviewOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• A targeted CRISPR-Cas9 mediated F0 screen identifies genes involved in establishment of the enteric nervous system

  PLoS ONE · 2024-05-29 · 8 citations

  articleOpen accessSenior authorCorresponding

  The vertebrate enteric nervous system (ENS) is a crucial network of enteric neurons and glia resident within the entire gastrointestinal tract (GI). Overseeing essential GI functions such as gut motility and water balance, the ENS serves as a pivotal bidirectional link in the gut-brain axis. During early development, the ENS is primarily derived from enteric neural crest cells (ENCCs). Disruptions to ENCC development, as seen in conditions like Hirschsprung disease (HSCR), lead to the absence of ENS in the GI, particularly in the colon. In this study, using zebrafish, we devised an in vivo F0 CRISPR-based screen employing a robust, rapid pipeline integrating single-cell RNA sequencing, CRISPR reverse genetics, and high-content imaging. Our findings unveil various genes, including those encoding opioid receptors, as possible regulators of ENS establishment. In addition, we present evidence that suggests opioid receptor involvement in the neurochemical coding of the larval ENS. In summary, our work presents a novel, efficient CRISPR screen targeting ENS development, facilitating the discovery of previously unknown genes, and increasing knowledge of nervous system construction.

  PublisherOA PDFDOI

• A targeted CRISPR-Cas9 mediated F0 screen identifies genes involved in establishment of the enteric nervous system

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-12-29 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract The vertebrate enteric nervous system (ENS) is a crucial network of enteric neurons and glia resident within the entire gastrointestinal tract (GI). Overseeing essential GI functions such as gut motility and water balance, the ENS serves as a pivotal bidirectional link in the gut-brain axis. During early development, the ENS is primarily derived from enteric neural crest cells (ENCCs). Disruptions to ENCC development, as seen in conditions like Hirschsprung disease (HSCR), lead to absence of ENS in the GI, particularly in the colon. In this study, using zebrafish, we devised an in vivo F0 CRISPR-based screen employing a robust, rapid pipeline integrating single-cell RNA sequencing, CRISPR reverse genetics, and high-content imaging. Our findings unveil various genes, including those encoding for opioid receptors, as possible regulators of ENS establishment. In addition, we present evidence that suggests opioid receptor involvement in neurochemical coding of the larval ENS. In summary, our work presents a novel, efficient CRISPR screen targeting ENS development, facilitating the discovery of previously unknown genes, and increasing knowledge of nervous system construction.

  PublisherOA PDFDOI

• Systematic analysis of proximal midgut‐ and anorectal‐originating contractions in larval zebrafish using event feature detection and supervised machine learning algorithms

  Neurogastroenterology & Motility · 2023-09-24 · 1 citations

  articleOpen access

  BACKGROUND: Zebrafish larvae are translucent, allowing in vivo analysis of gut development and physiology, including gut motility. While recent progress has been made in measuring gut motility in larvae, challenges remain which can influence results, such as how data are interpreted, opportunities for technical user error, and inconsistencies in methods. METHODS: To overcome these challenges, we noninvasively introduced Nile Red fluorescent dye to fill the intraluminal gut space in zebrafish larvae and collected serial confocal microscopic images of gut fluorescence. We automated the detection of fluorescent-contrasted contraction events against the median-subtracted signal and compared it to manually annotated gut contraction events across anatomically defined gut regions. Supervised machine learning (multiple logistic regression) was then used to discriminate between true contraction events and noise. To demonstrate, we analyzed motility in larvae under control and reserpine-treated conditions. We also used automated event detection analysis to compare unfed and fed larvae. KEY RESULTS: Automated analysis retained event features for proximal midgut-originating retrograde and anterograde contractions and anorectal-originating retrograde contractions. While manual annotation showed reserpine disrupted gut motility, machine learning only achieved equivalent contraction discrimination in controls and failed to accurately identify contractions after reserpine due to insufficient intraluminal fluorescence. Automated analysis also showed feeding had no effect on the frequency of anorectal-originating contractions. CONCLUSIONS & INFERENCES: Automated event detection analysis rapidly and accurately annotated contraction events, including the previously neglected phenomenon of anorectal contractions. However, challenges remain to discriminate contraction events based on intraluminal fluorescence under treatment conditions that disrupt functional motility.

  PublisherOA PDFDOI

Recent grants

• CAREER: Understanding spatiotemporal construction of vertebrate enteric nervous system

  NSF · $915k · 2020–2025

• Functional analysis of early vagal neural crest and ENS development

  NIH · $164k · 2014–2017

• NIH Grant F31EY019239

  NIH · $138k · 2013

Frequent coauthors

• Eileen W. Singleton

  Rice University

  13 shared

• Rodrigo Ibarra‐García‐Padilla

  Rice University

  8 shared

• Jeffrey M. Gross

  The University of Texas at Austin

  8 shared

• Aubrey G.A. Howard

  7 shared

• Phillip A. Baker

  Rice University

  6 shared

• Priya Ravisankar

  Allen Institute for Immunology

  6 shared

• Marianne Bronner‐Fraser

  California Institute of Technology

  6 shared

• Joshua Moore

  5 shared

Education

• PhD, Biology

  Graduate School, University of Texas, Austin

  2012

Awards & honors

• CPRIT Scholar in Cancer Research
• John S. Dunn Collaborative Research Award
• NSF CAREER Award