The homeodomain factor Lbx1 distinguishes two major programs of neuronal differentiation in the dorsal spinal cord
Open accessAbstract
Dorsal horn neurons in the spinal cord integrate and relay sensory information. Here, we show that the expression of the homeobox gene Lbx1 distinguishes two major neuronal classes generated in the dorsal spinal cord. The Lbx1(-) (class A) and Lbx1(+) (class B) neurons differ in their dependence on roof plate BMP signals for specification and settle in the deep and superficial dorsal horn, respectively. Lbx1 misexpression blocks the differentiation of class A neurons. Conversely, in Lbx1 mutant mice, class B neurons assume the identity of class A neurons. As a consequence, the morphology and neuronal circuitry of the dorsal horn are aberrant. We conclude that Lbx1 distinguishes two major neuronal classes in the dorsal spinal cord and is an important determinant of their distinct differentiation programs.
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The increase in dI4 and dI5 neurons is explained by the expansion of the combined dp4/dp5 progenitor pool in the dorsal spinal cord at these stages and the extended phase of neurogenesis in the dorsal spinal cord that results in late born dI4 and dI5 neurons.
“This is explained by the expansion of the combined dp4/dp5 progenitor pool in the dorsal spinal cord at these stages and the extended phase of neurogenesis in the dorsal spinal cord that results in the formation of late born dI4 and dI5 neurons”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Müller et al., 2002
The decrease in dorsal progenitors at e13.5 is in line with the higher rate of neurogenesis in the dorsal spinal cord at e13.5 and the consequent depletion of progenitors.
“This is in line with the higher rate of neurogenesis in the dorsal spinal cord at e13.5 and the consequent depletion of progenitors”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Müller et al., 2002
A subset of cells from the dorsal dI4.6/dI6 lineages contributed to most ventral inhibitory populations.
“A subset of cells from the dorsal dI4.6/dI6 lineages contributed to most ventral inhibitory populations, which was unexpected though there have been reports of scattered dI4 Ptf1a-derived cells in the embryonic and perinatal ventral horn103,104, and the very small dI6 population is known to be ventrally located105–107.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [106]
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- Authors
- Müller, T., Brohmann, H., Pierani, A., Heppenstall, P. A., Lewin, G. R., Jessell, T. M., & Birchmeier, C.
- Affiliations
- Max Delbrück Center (DE)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Birchmeier, Carmen
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-05
- Volume
- 34
- Issue
- 4
- Pages
- 551-562
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2139909837
- Cited by
- 368
- References
- 43
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 10 · 2023: 19 · 2022: 15 · 2021: 15 · 2020: 17 · 2019: 16 · 2018: 18 · 2017: 15 · 2016: 14 · 2015: 11 · 2014: 13 · 2013: 26 · 2012: 17
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 4095 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- SDL (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Frauen
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- Lbx1, homeobox genes, dorsal horn neurons, spinal cord, neuronal differentiation, roof plate, BMP signaling, sensory neurons, neuronal identity
- MeSH terms
- Afferent Pathways, Animals, Axons, Cell Differentiation, Chick Embryo, DNA-Binding Proteins, Mice, Mutant Strains, Mitosis, Muscle Proteins, Mutation, Nervous System Malformations, Spinal Nerve Roots, Stem Cells, Transcription Factors, Homeodomain Proteins, Gene Expression Regulation, Developmental, Cell Lineage, Body Patterning, Posterior Horn Cells, Avian Proteins, Animals, Genetically Modified, Mice, PAX7 Transcription Factor, Basic Helix-Loop-Helix Proteins
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