Neural stem cells (NSCs) are progenitor cells that generate neurons and glial cells. They have a crucial role in developing, regenerating, and repairing the central nervous system (CNS). But how a limited number of NSCs in developing CNS generate diverse types of differentiated neurons and glial cells is an active area of research.
We are interested in understanding how region-specific cellular diversity is generated in developing CNS. This critically relies on the precise coordination of cellular phenomena like quiescence, proliferation, differentiation, and apoptosis of NSCs. Misregulation of any of these processes results in developmental disorders and malignancies in humans.
We use Drosophila NSCs to understand how molecular and signaling mechanisms are integrated to generate cellular diversity in developing CNS. Drosophila NSCs (also called neuroblasts-NBs) bear a striking resemblance to their vertebrate counterparts. Therefore, NBs serves as an excellent system to understand how stem cells integrate different developmental cues during CNS patterning.
The research in our lab focus on understanding how cellular and numerical diversity is generated in developing CNS and is broadly divided into two areas:
#Cell Fate determination of NSCs.
The research in this theme focuses primarily on understanding how NSCs generate different numbers of neurons/glial cells in a region-specific manner in developing CNS.
#Generation of different cell types by NSCs.
The research in this theme focuses on how a single NSC can generate different variety of neurons and glial cells in the CNS.
1. Cell Fate determination of NSCs.
During brain development, NSCs integrates spatial, temporal, and sex-specific information/signals to take up different fates, listed below:
# Proliferation
# Asymmetric Cell Division.
#Apoptosis.
#Quiescence Entry/Exit
Understanding the molecular basis of how these decisions are taken at a cellular level will give insights into the following questions:
1-How do stem cells generate the required number of neuronal and glial progeny?
2-How the proliferation to differentiation switch is controlled in NSCs?
3-How the differentiated state of post-mitotic neurons is maintained?
What prevents the neurons from de-differentiating back into a pluripotent state, which will lead to excess cell division and tumor development?
4- How stem cell population is maintained?
Any change in cell type or cell number will affect the precision of the neural circuit assembly and, therefore, affect an organism's behavior, and in the worst-case scenario, it will result in a disease condition. For example, excess NSC proliferation or de-differentiation of their progeny will lead to brain tumors.
Similarly, premature differentiation of NSCs will lead to early exhaustion of the NSC pool, thereby affecting cellular diversity, organ size, and homeostasis.
NSC proliferation/Asymmetric cell division and differentiation
Regulation of NSC proliferation is essential for controlling cell number and temporal fate progression. Drosophila NSCs, like any other stem cell, undergo asymmetric cell division, which generates a self-renewing and differentiating daughter cell. This mode of cell division has a central role in cell fate determination by asymmetric partitioning of the apical and basal polarity markers, thereby giving distinct fates to these two daughter cells. It is to be noted that two daughter cells have a broadly similar transcriptional profile but respond differently to external signaling inputs, thereby contributing to the cellular diversity.
In this part of the work, we are taking a candidate gene approach to identify the factors that impact asymmetric cell division, cell differentiation, and cell fate.
NSC Apoptosis as a means to regulate cell number
Our work with Drosophila NSCs has elucidated how the Hox family of transcription factors plays a role in regulating cellular diversity. More specifically, we have investigated how Hox genes regulate neural stem cell apoptosis in different regions of developing CNS to regulate the number of neurons generated therein. In this part of the work, we continue to identify molecules playing a role in neurogenesis through the regulation of NSC apoptosis.
We are interested in understanding how region-specific cellular diversity is generated in developing CNS. This critically relies on the precise coordination of cellular phenomena like quiescence, proliferation, differentiation, and apoptosis of NSCs. Misregulation of any of these processes results in developmental disorders and malignancies in humans.
We use Drosophila NSCs to understand how molecular and signaling mechanisms are integrated to generate cellular diversity in developing CNS. Drosophila NSCs (also called neuroblasts-NBs) bear a striking resemblance to their vertebrate counterparts. Therefore, NBs serves as an excellent system to understand how stem cells integrate different developmental cues during CNS patterning.
The research in our lab focus on understanding how cellular and numerical diversity is generated in developing CNS and is broadly divided into two areas:
#Cell Fate determination of NSCs.
The research in this theme focuses primarily on understanding how NSCs generate different numbers of neurons/glial cells in a region-specific manner in developing CNS.
#Generation of different cell types by NSCs.
The research in this theme focuses on how a single NSC can generate different variety of neurons and glial cells in the CNS.
1. Cell Fate determination of NSCs.
During brain development, NSCs integrates spatial, temporal, and sex-specific information/signals to take up different fates, listed below:
# Proliferation
# Asymmetric Cell Division.
#Apoptosis.
#Quiescence Entry/Exit
Understanding the molecular basis of how these decisions are taken at a cellular level will give insights into the following questions:
1-How do stem cells generate the required number of neuronal and glial progeny?
2-How the proliferation to differentiation switch is controlled in NSCs?
3-How the differentiated state of post-mitotic neurons is maintained?
What prevents the neurons from de-differentiating back into a pluripotent state, which will lead to excess cell division and tumor development?
4- How stem cell population is maintained?
Any change in cell type or cell number will affect the precision of the neural circuit assembly and, therefore, affect an organism's behavior, and in the worst-case scenario, it will result in a disease condition. For example, excess NSC proliferation or de-differentiation of their progeny will lead to brain tumors.
Similarly, premature differentiation of NSCs will lead to early exhaustion of the NSC pool, thereby affecting cellular diversity, organ size, and homeostasis.
NSC proliferation/Asymmetric cell division and differentiation
Regulation of NSC proliferation is essential for controlling cell number and temporal fate progression. Drosophila NSCs, like any other stem cell, undergo asymmetric cell division, which generates a self-renewing and differentiating daughter cell. This mode of cell division has a central role in cell fate determination by asymmetric partitioning of the apical and basal polarity markers, thereby giving distinct fates to these two daughter cells. It is to be noted that two daughter cells have a broadly similar transcriptional profile but respond differently to external signaling inputs, thereby contributing to the cellular diversity.
In this part of the work, we are taking a candidate gene approach to identify the factors that impact asymmetric cell division, cell differentiation, and cell fate.
NSC Apoptosis as a means to regulate cell number
Our work with Drosophila NSCs has elucidated how the Hox family of transcription factors plays a role in regulating cellular diversity. More specifically, we have investigated how Hox genes regulate neural stem cell apoptosis in different regions of developing CNS to regulate the number of neurons generated therein. In this part of the work, we continue to identify molecules playing a role in neurogenesis through the regulation of NSC apoptosis.