development of the Enteric Nervous System

Using various lineage tracing and fate-mapping transgenic models, we study the development of the ENS during embryonic development, post-natal life, and in adulthood.

In addition, using next-generation tools of microscopy and mathematical modeling, we are working on elucidating the molecular and cellular pathways that generate the conserved structure and topology of the ENS, and study how aberration in these pathways alters ENS structure and function.

The development of the ENS is based on many yet unresolved and understudied factors such as gender and presence of microbiota and our lab is working on studying how innervation patterns of ENS developmentally change with alterations in microbiota between the two genders.

MAINTENANCE of the Enteric Nervous System

Previous dogma suggested a lack of steady state neurogenesis in the adult mammalian gut, leaving unanswered the question of how the adult ENS maintains itself, despite detectable neuronal loss.

In a pioneering work that we published in collaboration with the Pasricha Lab at JHU, we provided the first evidence of an active and rapid turnover of adult enteric neurons. By discovering the true identity of the Enteric Neural Stem Cells in adult gut, our team was the first to report on an active and a robust pathway of adult enteric neurogenesis.

 

Our work shows for the first time that the putative cause of gastrointestinal dysmotility is not neuronal deficits or dysfunctions but are pathological alterations in their precursor cells.

Our current work focuses on elucidating the cellular and molecular pathways that are associated with ealthy neurogenesis, along with studying the biotic and abiotic factors that alter it causing gastrointestinal dysmotility.

Adult myenteric ganglia showing neurons (red) and Nestin-expressing cells (Green). Intraganglionic Nestin-expressing cells effect continuous neurogenesis at steady state. Kulkarni et al 2017