Ectopic dendrite initiation: CNS pathogenesis as a model of CNS development
Abstract
The neuronal storage diseases are a rare group of disorders with profound clinical consequences including severe mental retardation and death in early childhood. A subset of these disorders, those with elevated levels of GM2 ganglioside, are further characterized by the reinitiation of primary dendrites on mature cortical neurons. These ectopic dendrites are unusual as primary dendrite initiation is normally confined to a narrow developmental window. Thus, ectopic dendritogenesis appears to be a recapitulation of the normal developmental program temporally displaced. Consequently, understanding ectopic dendritogenesis should offer insights into both the pathogenesis of the neuronal storage diseases as well as mechanisms of normal CNS development. Using a feline model of GM2 gangliosidosis, we compared patterns of gene expression in normal newborn and mature diseased animals (both undergoing active primary dendritogenesis) with normal, mature controls (where primary dendritogenesis has ceased). From this work, we have identified two genes that appear to function in primary dendrite initiation. One, tomoregulin, is an integral membrane protein with both EGF‐ and follistatin‐like motifs in its extracellular domain. The second, Tristanin, is a member of the positive regulatory domain (PRD) family of a zinc‐finger transcription factors. Both genes are up regulated in the disease state, and both show a shift in their intracellular location to the nucleus in diseased animals that is not observed in age matched controls. In normal mouse brain, tomoregulin and Tristanin reveal developmental patterns consistent with a role in dendrite initiation and show changes in subcellular localization similar to that observed in the cat.
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PRDM10 may be related to dendrite growth and neural crest related changes that contributed to the formation of our distinct modern face.
“Although little is known about PRDM10, it may be related to dendrite growth147 and neural crest related changes that contributed to the formation of our distinct modern face148.”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [147]
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A catalog of single nucleotide changes distinguishing modern humans from archaic hominins
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- Authors
- Siegel, D. A., Huang, M. K., & Becker, S. F.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Siegel, Donald A.
- Venue
- International Journal of Developmental Neuroscience
- Publisher
- Wiley
- Published
- 2002-06
- Volume
- 20
- Issue
- 3-5
- Pages
- 373-389
- ISSN
- 0736-5748 (ISSN-L)
- 1873-474X
- OpenAlex
- W2064396478
- Cited by
- 26
- References
- 54
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 2 · 2015: 4 · 2013: 3 · 2012: 1
- FWCI
- 0.20
- Type
- journal article
- Language
- en
- Update notices
- erratum (2003-04-08)
- Open access
- closed
- Locations
- International Journal of Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- March of Dimes Birth Defects Foundation (12-FY99-274)
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- GM2 gangliosidosis, GM2 ganglioside, gene expression, subcellular localization, nuclear translocation, central nervous system development, feline model, cortical neurons
- MeSH terms
- Animals, Animals, Newborn, Cats, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Dendrites, Disease Models, Animal, DNA-Binding Proteins, Fetus, Genetic Testing, Immunohistochemistry, Membrane Proteins, Mice, Inbred C57BL, Molecular Sequence Data, Neoplasm Proteins, RNA, Messenger, Sequence Homology, Nucleic Acid, Transcription Factors, Sequence Homology, Amino Acid, Pyramidal Cells, DNA, Complementary, Gangliosidoses, GM2, Mice
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