Robust control of mitotic spindle orientation in the developing epidermis.

Area of Science:

• Cell biology
• Developmental biology
• Skin biology

Background:

• Progenitor cells balance self-amplification and differentiation.
• Epidermal progenitors divide symmetrically for growth and asymmetrically for stratification.
• The regulation of these division modes is crucial for tissue homeostasis.

Purpose of the Study:

• To investigate the regulatory mechanisms controlling cell division modes in epidermal progenitors.
• To identify key molecular players that determine symmetric versus asymmetric cell division (ACD).
• To understand how division orientation is controlled to maintain epidermal structure.

Main Methods:

• Analysis of cell division in mouse epidermis.
• Investigating the role of the mouse Inscuteable gene in division orientation.
• Examining the localization and function of NuMA in spindle orientation.
• Assessing the role of p63 in regulating cell division modes.

Main Results:

• Individual epidermal cells can switch between symmetric and asymmetric division modes.
• Inscuteable expression is sufficient to induce ACD in epidermal progenitors.
• NuMA localization changes prevent excessive ACDs by controlling spindle orientation.
• The transcriptional regulator p63 does not influence division mode or orientation.

Conclusions:

• Two key regulatory points controlling ACD in the epidermis have been identified: Inscuteable and NuMA localization.
• These findings provide a framework for understanding how external cues influence cell division choices in the epidermis.
• The balance of division modes is determined by the sum of individual cell choices, regulated by specific molecular mechanisms.