Sive Lab

Neurodevelopmental and Mental Health Disorders

One aspect of our research focuses on addressing human disorders.

  • Neurodevelopmental disorders
    • Epilepsy
    • 16p11.2
    • Pitt-Hopkins Syndrome
    • Autism Spectrum Disorders
    • Hydrocephalus
    • Psychiatric disorders

One day old zebrafish embryo

The brain ventricular system (red) contains cerebrospinal fluid, which circulates throughout the brain and spinal cord. This fluid provides buoyancy and cushioning to protect the nervous tissue, as well as bringing nutrients and removing waste.

Transgenic zebrafish

Two day old transgenic zebrafish show green fluorescent protein to mark where certain neuron types are born in the eye, the nose, and certain parts of the brain.

Transgenic zebrafish

Two day old transgenic zebrafish show green fluorescent protein to mark where certain neuron types are born in the eye, the nose, and certain parts of the brain.

Axon tracts are bundles of nerve fibers that connect different regions of the brain to one another and to the spinal cord. The tracts are labeled here in green in 1.5 day old zebrafish embryos

Axon tracts

Axon tracts are bundles of nerve fibers that connect different regions of the brain to one another and to the spinal cord. The tracts are labeled here in green in 1.5 day old zebrafish embryos

Neurodevelopmental and Mental Health Disorders

Understanding the causes of neurodevelopmental and mental health disorders is one of the greatest clinical challenges. We established use of zebrafish for analysis of neurodevelopmental disorders, including focus on the schizophrenia risk gene DISC1 and Pitt-Hopkins Syndrome, a rare monogenic disorder. We are presently addressing 16p11.2 deletion (16pdel) syndrome, a penetrant and severe haploinsufficient syndrome that is tightly associated with autism, intellectual disability, seizures, obesity, hyperactivity and hypotonia. The 16p11.2 region contains 25 genes, and genetic data indicate that two or more genes synergize in symptomatology. We defined the first functional genetic interactome for 16pdel syndrome, and recent work implicates alteration of lipid metabolism in 16pdel-relevant phenotypes.

 

  1. DeRienzo, G., Bishop, J. A., Mao, Y., Pan, L., Ma, T.P., Moens, C.B., Tsai, L.H. and Sive, H. Disc1 regulates both b-catenin-mediated and non-canonical Wnt signaling during vertebrate embryogenesis. FASEB J. 25: 4184-4197, 2011.
  2. *Blaker-Lee, A., *Gupta, S., *McCammon, J., De Rienzo, G. and  Sive, H.   Zebrafish homologs of 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes. *Equal contribution.  Dis. Model. Mech.  5: 834-851, 2012.
  3. McCammon, J.M., Blaker-Lee, A., Chen, X. and Sive, H.  The 16p11.2 homologs fam57ba and doc2a generate certain brain and body phenotypes, Hum. Mol. Genet. 26: 3699-3712, 2017.
  4. Tomasello,, D.L,  Kim, J.L., Khodour, Y., McCammon, J.M., Mitalipova, M., Rudolf Jaenisch, R., Futerman,  A.H., Sive, H. 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis. iScience. 25(1):103551 2022 PMID: 34984324