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Neurulation in the cranial region--normal and abnormal.

Andrew J Copp1

  • 1Neural Development Unit, Institute of Child Health, University College London, UK. a.copp@ich.ucl.ac.uk

Journal of Anatomy
|November 30, 2005
PubMed
Summary

Cranial neurulation forms the brain primordium through dorsolateral bending and midline fusion. Defects in this process, often linked to molecular signaling pathways, can lead to neural tube defects like exencephaly.

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Area of Science:

  • Developmental Biology
  • Embryology
  • Genetics

Background:

  • Cranial neurulation is essential for forming the brain primordium in vertebrate embryos.
  • This process involves complex morphogenetic events, including neural fold closure and fusion, with variations observed across species and strains.
  • Neural tube defects, such as exencephaly, occur during this critical developmental period and show sex-based incidence differences.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying cranial neurulation and identify factors critical for normal neural tube closure.
  • To analyze the genetic and cellular requirements for dorsolateral bending, a key event in cranial neural tube formation.
  • To explore the role of specific signaling pathways, like planar cell polarity, in preventing severe neurulation defects.

Main Methods:

  • Analysis of various mouse strains, including wild-type and mutant models with gene-targeted defects.
  • Detailed observation and characterization of cranial neurulation processes, focusing on neural fold dynamics and fusion.
  • Molecular and cellular analyses to identify genetic and biochemical factors influencing neurulation, including cytoskeleton function, cell migration, apoptosis, and differentiation.

Main Results:

  • Normal cranial neurulation requires a functional actin cytoskeleton, cranial neural crest cell emigration, regulated apoptosis, and balanced cell proliferation/differentiation.
  • Defects in dorsolateral bending are associated with disruptions in these cellular and molecular processes.
  • Craniorachischisis, a severe combined brain and spine defect, is linked to disruptions in the planar cell polarity signaling pathway.

Conclusions:

  • Dorsolateral bending is a crucial, multi-factorial event in cranial neurulation, dependent on coordinated cellular activities and molecular signaling.
  • Disruptions in key cellular processes or signaling pathways, such as planar cell polarity, can lead to significant neural tube defects.
  • Understanding these mechanisms is vital for comprehending the etiology of congenital brain and spinal malformations.

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