The amygdala is a formation of interconnected nuclei essential for encoding the emotional and motivational components of behavior, learning, and memory. Perturbations of amygdala development are thought to contribute to many neuropsychiatric disorders, but neither the timing of nor the precise cellular substrates subject to these perturbations are well understood. Consequently, assessing the molecular identities and developmental programs governing the amygdala is essential for understanding the etiology of neuropsychiatric disease. Here, I propose to decipher the gene regulatory networks necessary for the development of the basolateral amygdala complex (BLA), a group of nuclei comprised largely of glutamatergic cells that serve as the primary functional input to the amygdala. Studies from our laboratory have identified transcription factors that play critical roles in the development of glutamatergic neurons, similar to those that populate the amygdala. In this proposal I will focus on one transcription factor, characterizing its role in the migration and survival of different types of BLA glutamatergic neurons and identify its downstream effectors. To do so, I will use a conditional knockout mouse and conduct single nuclear RNA sequencing (snRNA-Seq), chromatin immunoprecipitation followed by sequencing (ChIP-seq), and validation experiments of candidate downstream effectors. Cellular, molecular, and genomic techniques are well established in the Sestan laboratory, and this expertise will allow me to both elucidate the molecular processes governing BLA glutamatergic projection neuron specification and identity and aid in deciphering the relevant developmental context underlying numerous neuropsychiatric disorders.
This proposal will determine the transcriptional regulatory networks that govern the development, cell-type specification, and cell-type identity of the amygdala, a brain region critical in numerous neuropsychiatric and neurodevelopmental disorders. Because the molecular mechanisms underlying the formation of the amygdala are extremely understudied, this work is essential for deciphering the relevant developmental context that underlies neuropsychiatric disorders.
