SCCPDH regulates early brain development in zebrafish

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NHGRI	DEVBIO-1

* FARE Award Winner

Authors

• E.A. Burke
• W.A. Gahl
• C.F. Boerkoel

Abstract

SCCPDH is a human nuclear envelope transmembrane-associated protein that currently has no known function. SCCPDH lies within the critical region for the 1q44 microdeletion syndrome, which is characterized by intellectual disability, developmental delay and brain anomalies. We hypothesized therefore that SCCPDH contributes to brain development. Testing this by morpholino knockdown of the zebrafish homologue, we observed a dose-dependent loss of brain tissue at the midbrain-hindbrain boundary, decreased eye size, and hydrocephalus. This morphant phenotype was rescued by co-injection of wild type SCCPDH mRNA in over 80% of embryos. Overexpression of wild type mRNA in zebrafish resulted in an increased incidence of cyclopia and abnormal forebrain development. In situ hybridization and gene expression array analyses of SCCPDH morphants found deregulated gene expression including overexpression of pax2 in the optic primordia and reduced expression of dlx2a, otx2, and gsc in the forebrain and midbrain at 24 hours post fertilization. Moreover, the array data showed a significant increase in the expression of p53 and other apoptosis-related genes as well as significant expression alterations within the TGF-β, canonical Wnt, and Delta-Notch signaling pathways. These results confirm a role for SCCPDH in brain formation and suggest that it modulates the expression of key developmental pathways.

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