Cellular and molecular mechanisms of early brain wiring

We are studying a family of transcription factors, nuclear factor one (Nfi), which play critical roles in early brain development.  Children with mutations in Nfi genes display a variety of developmental disorders that form part of syndromes that include intellectual disability and other cognitive disorders. Nfi genes regulate progenitor cell development and are crucially important for the development of midline glial populations that regulate interhemispheric remodeling of the septum, which provides a substrate for callosal axons to cross the midline.  The Nfi genes also regulate neuronal development, and we are interested in how they regulate brain development at both a cellular and molecular level.

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We study the function of Nfi transcription factors in mice and in human-derived pluripotent stem cells. Using various sequencing (ATAC-Seq, RNA-Seq, ChIP-Seq), histological and molecular techniques, as well as in utero electroporation combined with birth dating studies we seek to answer:

1. How NFI binding regulates chromatin accessibility and the epigenetic state of regulatory elements driving cell differentiation during development.

2. How binding affects the function of other transcription factors critical for progenitor cell differentiation.

3. How candidate genes that are found in human CCD patients interact with Nfi transcription factors.