About

Hazel Sive is a Professor Emerita and Dean of Science at Northeastern University, with a history of affiliation with MIT. Her research focuses on fundamental mechanisms underlying vertebrate development, particularly face and brain formation, as well as the molecular underpinnings of neurodevelopmental disorders. Her lab probes molecular mechanisms involving the Extreme Anterior Domain, a facial signaling center that also forms the mouth, and examines the brain ventricular system and a novel cell shape change called basal constriction in the brain. Additionally, her work addresses neurodevelopmental disorders such as autism spectrum disorders, intellectual disability, and epilepsy, aiming to define novel therapeutics. Professor Sive has contributed significantly to understanding craniofacial and brain development through her studies on signaling pathways and cellular processes. She has been recognized with awards including the School of Science Teaching Prize in 2020 and the Margaret MacVicar Faculty Fellowship from 2015 to 2025. Her research has advanced knowledge of cerebrospinal fluid movement, craniofacial organizer functions, and the genetic basis of brain and body phenotypes, making her a prominent figure in developmental biology and neurobiology.

Research topics

• Biology
• Cell biology
• Anatomy
• Genetics
• Neuroscience

Selected publications

• Common DISC1 Polymorphisms Disrupt Wnt/GSK3β Signaling and Brain Development

  Neuron · 2025-05-01 · 1 citations

  erratumOpen access
  PublisherOA PDFDOI

• A Hypothesis: Metabolic Contributions to 16p11.2 Deletion Syndrome

  BioEssays · 2024-12-29 · 1 citations

  reviewOpen accessSenior authorCorresponding

  16p11.2 deletion syndrome is a severe genetic disorder associated with the deletion of 27 genes from a Copy Number Variant region on human chromosome 16. Symptoms associated include cognitive impairment, language and motor delay, epilepsy or seizures, psychiatric disorders, autism spectrum disorder (ASD), changes in head size and body weight, and dysmorphic features, with a crucial need to define genes and mechanisms responsible for symptomatology. In this review, we analyze the clinical associations and biological pathways of 16p11.2 locus genes and identify that a majority of 16p11.2 genes relate to metabolic processes. We present a hypothesis in which changes in the dosage of 16p11.2 metabolic genes contribute to pathology through direct or indirect alterations in pathways that include amino acids or proteins, DNA, RNA, catabolism, lipid, energy (carbohydrate). This hypothesis suggests that research into the specific roles of each metabolic gene will help identify useful therapeutic targets.

  PublisherOA PDFDOI

• Obtaining<i>Xenopus</i>Eggs and Embryos

  Cold Spring Harbor Protocols · 2022-10-25 · 4 citations

  review1st authorCorresponding

  Collecting eggs from adult Xenopus laevis and Xenopus tropicalis to raise healthy embryos and tadpoles is relatively simple but requires careful handling of the frog. Eggs can be fertilized through natural matings or by in vitro fertilization and examined visually. Here we review how eggs are obtained and how to recognize healthy eggs that will develop into high-quality embryos.

  PublisherDOI

• Craniofacial Development and Disorders—Contributions of Xenopus

  2022-03-17 · 1 citations

  book-chapterOpen accessSenior author

  In people and other vertebrates, craniofacial development leads to formation of the skull, facial bones, and cartilage. Craniofacial development is complex, involving multiple cell types, with carefully coordinated cell movements, and is often disrupted, with disorders occurring in ~1/700 of live human births. The frog Xenopus has proven an outstanding model for understanding mechanisms of craniofacial development. Neural crest cells are unique to vertebrates and contribute a large part of the craniofacial skeleton. The mouth is conserved and essential, arising from ectodermal and endodermal cells. Multiple signaling pathways and regulatory genes are required for craniofacial development, including a major signaling center, the extreme anterior domain. Present treatments of craniofacial disorders are largely surgical. The need for definition of genes and molecular mechanisms underlying craniofacial disorders is critical and an area in which Xenopus is making key contributions. Xenopus remains one of the most accessible systems for uncovering connections to human craniofacial disorders.

  PublisherOA PDFDOI

• <i>Xenopus</i>Husbandry

  Cold Spring Harbor Protocols · 2022-09-27

  articleSenior author

  Adult frogs that are well-cared-for will give high-quality eggs and embryos for use in every Xenopus protocol. Thoughtful frog husbandry is thus pivotal to successful research using these organisms. Protocols for successfully raising tadpoles, establishing and maintaining water quality, and detecting specific pathogens are key to maintaining healthy frog populations.

  PublisherDOI

• 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis

  iScience · 2021-12-02 · 26 citations

  articleOpen accessSenior authorCorresponding

  contributes to changes in neuronal activity and function in 16pdel syndrome through a crucial role for the gene in lipid metabolism.

  PublisherOA PDFDOI

• The 16p11.2-Linked Gene,&amp;nbsp; &lt;i&gt;FAM57B&lt;/i&gt;&amp;nbsp;Encodes a Modulator of Ceramide Synthesis that Regulates Lipid Levels and Synaptic Composition in the Developing Brain

  SSRN Electronic Journal · 2021-01-01

  articleOpen accessSenior author
  PublisherDOI

• FAM57B is a modulator of ceramide synthesis that regulates sphingolipid homeostasis and synaptic composition in the developing brain

  bioRxiv (Cold Spring Harbor Laboratory) · 2021-03-02 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Abstract The complex 16p11.2 Deletion Syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder and intellectual disability. We demonstrate that 16pdel iPSC differentiated neurons showed augmented local field potential activity and altered ceramide-related lipid species relative to unaffected. FAM57B , a poorly characterized gene in the 16p11.2 interval, has emerged as a candidate tied to symptomatology. We found that FAM57B modulates ceramide synthase (CerS) activity, but is not a CerS per se. In FAM57B mutant human neuronal cells and zebrafish brain, composition and levels of sphingolipids and glycerolipids associated with cellular membranes are disrupted. Consistently, we observed aberrant plasma membrane architecture and synaptic protein mislocalization, which were accompanied by depressed brain and behavioral activity. Together, these results suggest that haploinsufficiency of FAM57B contributes to changes in neuronal activity and function in 16pdel Syndrome, through a crucial role for the gene in lipid metabolism.

  PublisherOA PDFDOI

• Regulation of Head Size by the Extreme Anterior Domain: A Target for Microcephaly

  SSRN Electronic Journal · 2020-01-01

  articleOpen accessSenior author
  PublisherDOI

• Mouth development

  UNC Libraries · 2020-04-22

  articleOpen access

  A mouth is present in all animals, and comprises an opening from the outside into the oral cavity and the beginnings of the digestive tract to allow eating. This review focuses on the earliest steps in mouth formation. In the first half, we conclude that the mouth arose once during evolution. In all animals, the mouth forms from ectoderm and endoderm. A direct association of oral ectoderm and digestive endoderm is present even in triploblastic animals, and in chordates, this region is known as the extreme anterior domain (EAD). Further support for a single origin of the mouth is a conserved set of genes that form a 'mouth gene program' including foxA and otx2. In the second half of this review, we discuss steps involved in vertebrate mouth formation, using the frog Xenopus as a model. The vertebrate mouth derives from oral ectoderm from the anterior neural ridge, pharyngeal endoderm and cranial neural crest (NC). Vertebrates form a mouth by breaking through the body covering in a precise sequence including specification of EAD ectoderm and endoderm as well as NC, formation of a 'pre-mouth array,' basement membrane dissolution, stomodeum formation, and buccopharyngeal membrane perforation. In Xenopus, the EAD is also a craniofacial organizer that guides NC, while reciprocally, the NC signals to the EAD to elicit its morphogenesis into a pre-mouth array. Human mouth anomalies are prevalent and are affected by genetic and environmental factors, with understanding guided in part by use of animal models. WIREs Dev Biol 2017, 6:e275. doi: 10.1002/wdev.275 For further resources related to this article, please visit the WIREs website.

  PublisherDOI

Recent grants

• NIH Grant R01MH077253

  NIH · $439k · 2010

• METABOLIC CHANGES UNDERLYING 16P11.2 DELETION SYNDROME

  NIH · $436k · 2020–2023

• The Extreme Anterior Domain and Face Formation

  NIH · $4.5M · 2010–2023

• NIH Grant R21DE017758

  NIH · $529k · 2008

• NIH Grant R21MH070926

  NIH · $466k · 2006

Frequent coauthors

• Laura Anne Jacox

  39 shared

• Richard M. Harland

  University of California, Berkeley

  36 shared

• David P. Bartel

  Whitehead Institute for Biomedical Research

  35 shared

• Jessica T. Chang

  Discovery Institute

  31 shared

• Laura Anne Lowery

  25 shared

• Joshua T. Gamse

  Genmab (United States)

  25 shared

• Jennifer H. Gutzman

  University of Wisconsin–Milwaukee

  23 shared

• Robert M. Grainger

  University of Virginia

  23 shared

Labs

• Sive LabPI

Education

• Ph.D.

  Rockefeller University

  1986

• B.Sc. (Chemistry, Zoology) B.Sc Hons (Zoology), Chemistry, Zoology

  University of the Witwatersrand

  1979

Awards & honors

• School of Science Teaching Prize, 2020
• Margaret MacVicar Faculty Fellow, 2015 - 2025