The Notch effector gene Hes1 regulates migration of hypothalamic neurons, neuropeptide content and axon targeting to the pituitary

Autor: Paven K. Aujla, Jonathan V. Sweedler, Adriana Bora, Pamela Monahan, Lori T. Raetzman
Rok vydání: 2011
Předmět:
Male
Vasopressin
Supraoptic nucleus
Mice
Diencephalon
0302 clinical medicine
Cell Movement
Basic Helix-Loop-Helix Transcription Factors
Axon
Neurons
0303 health sciences
Stem Cells
SS
medicine.anatomical_structure
Hypothalamus
Pituitary Gland
AVP
embryonic structures
Female
Supraoptic Nucleus
hormones
hormone substitutes
and hormone antagonists
congenital
hereditary
and neonatal diseases and abnormalities
endocrine system
medicine.medical_specialty
Notch
Molecular Sequence Data
Notch signaling pathway
Neuropeptide
Development
Biology
Article
03 medical and health sciences
Internal medicine
In Situ Nick-End Labeling
medicine
Animals
Amino Acid Sequence
Molecular Biology
030304 developmental biology
Homeodomain Proteins
Cell Biology
SON
Axons
Hes1
Arginine Vasopressin
Mice
Inbred C57BL
Endocrinology
nervous system
Transcription Factor HES-1
PVN
Nucleus
030217 neurology & neurosurgery
Paraventricular Hypothalamic Nucleus
Developmental Biology
Zdroj: Developmental Biology. 353:61-71
ISSN: 0012-1606
DOI: 10.1016/j.ydbio.2011.02.018
Popis: Proper development of the hypothalamic-pituitary axis requires precise neuronal signaling to establish a network that regulates homeostasis. The developing hypothalamus and pituitary utilize similar signaling pathways for differentiation in embryonic development. The Notch signaling effector gene Hes1 is present in the developing hypothalamus and pituitary and is required for proper formation of the pituitary, which contains axons of arginine vasopressin (AVP) neurons from the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). We hypothesized that Hes1 is necessary for the generation, placement and projection of AVP neurons. We found that Hes1 null mice show no significant difference in cell proliferation or death in the developing diencephalon at embryonic day 10.5 (e10.5) or e11.5. By e16.5, AVP cell bodies are formed in the SON and PVN, but are abnormally placed, suggesting that Hes1 may be necessary for the migration of AVP neurons. GAD67 immunoreactivity is ectopically expressed in Hes1 null mice, which may contribute to cell body misplacement. Additionally, at e18.5 Hes1 null mice show continued misplacement of AVP cell bodies in the PVN and SON and additionally exhibit abnormal axonal projection. Using mass spectrometry to characterize peptide content, we found that Hes1 null pituitaries have aberrant somatostatin (SS) peptide, which correlates with abnormal SS cells in the pituitary and misplaced SS axon tracts at e18.5. Our results indicate that Notch signaling facilitates the migration and guidance of hypothalamic neurons, as well as neuropeptide content.
Databáze: OpenAIRE
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