Debadrita Bhattacharya

All Publications

• Neural crest metabolism: At the crossroads of development and disease DEVELOPMENTAL BIOLOGY Bhattacharya, D., Khan, B., Simoes-Costa, M. 2021; 475: 245-255

  Abstract

  The neural crest is a migratory stem cell population that contributes to various tissues and organs during vertebrate embryonic development. These cells possess remarkable developmental plasticity and give rise to many different cell types, including chondrocytes, osteocytes, peripheral neurons, glia, melanocytes, and smooth muscle cells. Although the genetic mechanisms underlying neural crest development have been extensively studied, many facets of this process remain unexplored. One key aspect of cellular physiology that has gained prominence in the context of embryonic development is metabolic regulation. Recent discoveries in neural crest biology suggest that metabolic regulation may play a central role in the formation, migration, and differentiation of these cells. This possibility is further supported by clinical studies that have demonstrated a high prevalence of neural crest anomalies in babies with congenital metabolic disorders. Here, we examine why neural crest development is prone to metabolic disruption and discuss how carbon metabolism regulates developmental processes like epithelial-to-mesenchymal transition (EMT) and cell migration. Finally, we explore how understanding neural crest metabolism may inform upon the etiology of several congenital birth defects.

  View details for DOI 10.1016/j.ydbio.2021.01.018

  View details for Web of Science ID 000651137900006

  View details for PubMedID 33548210

• Metabolic Reprogramming Promotes Neural Crest Migration via Yap/Tead Signaling DEVELOPMENTAL CELL Bhattacharya, D., Azambuja, A., Simoes-Costa, M. 2020; 53 (2): 199-+

  Abstract

  The Warburg effect is one of the metabolic hallmarks of cancer cells, characterized by enhanced glycolysis even under aerobic conditions. This physiological adaptation is associated with metastasis , but we still have a superficial understanding of how it affects cellular processes during embryonic development. Here we report that the neural crest, a migratory stem cell population in vertebrate embryos, undergoes an extensive metabolic remodeling to engage in aerobic glycolysis prior to delamination. This increase in glycolytic flux promotes Yap/Tead signaling, which activates the expression of a set of transcription factors to drive epithelial-to-mesenchymal transition. Our results demonstrate how shifts in carbon metabolism can trigger the gene regulatory circuits that control complex cell behaviors. These findings support the hypothesis that the Warburg effect is a precisely regulated developmental mechanism that is anomalously reactivated during tumorigenesis and metastasis.

  View details for DOI 10.1016/j.devcel.2020.03.005

  View details for Web of Science ID 000526953300009

  View details for PubMedID 32243782

  View details for PubMedCentralID PMC7236757

• Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis ELIFE Bhattacharya, D., Rothstein, M., Azambuja, A., Simoes-Costa, M. 2018; 7

  Abstract

  A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells. Our results show that a regulatory circuit formed by Wnt, Lin28a and let-7 miRNAs controls the deployment and the subsequent silencing of the multipotency program in a position-dependent manner. Transition from multipotency to differentiation is determined by the topological relationship between the migratory cells and the dorsal neural tube, which acts as a Wnt-producing stem cell niche. Our findings highlight a mechanism that rapidly silences complex regulatory programs, and elucidate how transcriptional networks respond to positional information during cell differentiation.

  View details for DOI 10.7554/eLife.40556

  View details for Web of Science ID 000453819200001

  View details for PubMedID 30520734

  View details for PubMedCentralID PMC6301792

• The molecular basis of neural crest axial identity DEVELOPMENTAL BIOLOGY Rothstein, M., Bhattacharya, D., Simoes-Costa, M. 2018; 444: S170-S180

  Abstract

  The neural crest is a migratory cell population that contributes to multiple tissues and organs during vertebrate embryonic development. It is remarkable in its ability to differentiate into an array of different cell types, including melanocytes, cartilage, bone, smooth muscle, and peripheral nerves. Although neural crest cells are formed along the entire anterior-posterior axis of the developing embryo, they can be divided into distinct subpopulations based on their axial level of origin. These groups of cells, which include the cranial, vagal, trunk, and sacral neural crest, display varied migratory patterns and contribute to multiple derivatives. While these subpopulations have been shown to be mostly plastic and to differentiate according to environmental cues, differences in their intrinsic potentials have also been identified. For instance, the cranial neural crest is unique in its ability to give rise to cartilage and bone. Here, we examine the molecular features that underlie such developmental restrictions and discuss the hypothesis that distinct gene regulatory networks operate in these subpopulations. We also consider how reconstructing the phylogeny of the trunk and cranial neural crest cells impacts our understanding of vertebrate evolution.

  View details for DOI 10.1016/j.ydbio.2018.07.026

  View details for Web of Science ID 000464483000014

  View details for PubMedID 30071217

  View details for PubMedCentralID PMC6355384