Dr. Ramkumar Sambasivan - Research
Animals of the same taxonomic group share a stereotypical spatial pattern of tissues and organs in their body. This is known as the body plan. Generating the animal body plan requires positional information in space and time during embryonic development. Gastrulation, the earliest patterning event during development, generates the 3 germ layers in correct spatial order i.e., inner gut-forming endoderm, outer ectoderm generating skin and the mesoderm layer forming muscle, bone etc. in between. Concomitant to gastrulation, the identities of presumptive head and tail are established, which entails the formation of the anterior-posterior (A/P) axis. Together with the orthogonal dorsal-ventral (D/V) axis, the A/P axis provides the spatial template for patterning the germ layers. The coordinates along the axes are created by variations in signaling microenvironments and transcription factor expression, which provide the embryonic positioning system for sculpting the body plan. The research program we have established in my laboratory tackles the patterning of mesoderm germ layer along the A/P axis.
We study the role of signaling pathways such as Wnt - b catenin and Nodal (a TGF-b family member) in providing the positional information for mesoderm patterning. One of our interests is to understand the mechanism specifying the anterior mesoderm, which generates muscles of the head and heart. We also explore the possibility of a transcription factor code in patterning i.e., differentially specifying mesoderm along A/P axis. Specifically, we investigate whether differential functions of three mesoderm T-box factors contribute to the specification of two distinct lineages of mesoderm; 1) mesendoderm, an early lineage, which originates along with endoderm and 2) neuromesoderm, which specifically contributes to elongation of body axis by making neural tube and mesoderm at the posterior end. In essence, the program aims to shed light on the molecular developmental mechanisms governing early patterning of vertebrate mesoderm along the A/P axis.
The emerging idea in the field is that the Wnt - b catenin signaling is a deeply conserved mechanism in the animal phylogeny for establishing anterior-posterior axis. As we uncover the mechanisms patterning vertebrate mesoderm, we plan to address their evolutionary conservation. Investigation of deep homology in developmental mechanisms could provide insights into the fundamentally conserved aspects of body plan across chordates, and eventually, in bilaterians.
In addition to our main interest in developmental mechanisms governing mesoderm specification, we study a specific aspect of neural crest biology. Neural crest cells are of ectodermal origin; in the head they emerge from the border of developing brain. Remarkably, head neural crest has a dual germ layer potential. They generate ectoderm derivatives such as neurons and glia of cranial ganglia and pigment cells as well as typical ‘mesodermal’ derivatives such as supportive skeleton and dermis of vertebrate head. We aim to understand the mechanisms governing the ‘mesodermal’ function of head neural crest. Head is a novel addition to vertebrate body plan, which enabled a dramatic transition from filter feeding to active predation. Anterior mesoderm with cardiac and myogenic potential and head neural crest with mesodermal character are central to the evolution of vertebrate head. This broader context integrates the two interests of our laboratory.