Dehydroepiandrosterone biosynthesis, role, and mechanism of action in the developing neural tube

Frontiers in Endocrinology, 2012 · DOI: 10.3389/fendo.2012.00016 · Published: February 7, 2012

Simple Explanation

Dehydroepiandrosterone (DHEA) is a hormone synthesized in the developing nervous system. This study investigates the role of DHEA in the developing spinal cord, specifically its influence on the growth and specialization of nerve cells. The researchers found that DHEA promotes the production of specific proteins (Nkx6.1, Olig-2, and Isl-1/2) that are important for the development of motor neurons, which control muscle movement. DHEA also encourages the growth of neural precursor cells, the cells that give rise to neurons. Further experiments revealed that DHEA's effects are dependent on the Sonic hedgehog (Shh) signaling pathway, a crucial communication system for cell development. This suggests that DHEA works in conjunction with Shh to regulate the development of the spinal cord.

Study Duration

Not specified

Participants

CD-1 mice embryos

Evidence Level

Not specified

Key Findings

1
DHEA induces the expression of class II protein Nkx6.1, motor neuron precursor Olig-2, and deﬁnitive motor neuron marker Isl-1/2 in vitro.
2
DHEA also promoted proliferation of ventrally committed precursors in isolated spinal cord precursor cultures and in whole spinal cord explants.
3
Both the proliferative and inductive effects of DHEA were dependent on sonic hedgehog signaling.

Research Summary

This study establishes that DHEA is biosynthesized in the developing ventral neural tube at the time of neurogenesis and cell fate determination. In in vitro models, DHEA modulated the induction of expression of Nkx6.1, a class II homeodomain protein, as well as expression of the homeodomain proteins Olig-2, a speciﬁc motor neuron precursor marker, and Isl-1/2, a deﬁnitive motor neuron marker. Moreover, DHEA promoted proliferation of ventral neuronal progenitors committed into the derepression cascade leading to the generation of motor neurons. Both of these biological actions of DHEA are dependent on Shh.

Practical Implications

Understanding Neural Development

This research contributes to our understanding of the complex interplay of factors that govern neural tube development, particularly the role of neurosteroids like DHEA.

Potential Therapeutic Applications

The findings may have implications for future therapeutic strategies aimed at promoting neural regeneration or treating spinal cord injuries by manipulating DHEA and Shh signaling.

Biological Clock Mechanism

The study supports the idea that DHEA biosynthesis acts as a biological clock, controlling the timing and extent of neuronal-precursor proliferation in the developing neural tube.

Study Limitations

1
The study relies heavily on in vitro models, which may not fully replicate the complex environment of the developing neural tube in vivo.
2
The exact mechanisms by which DHEA interacts with the Shh signaling pathway remain to be fully elucidated.
3
Conditional knock-out of P450c17 enzyme is needed to confirm these observations in an in vivo model.

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