The cerebellum is central nervous system key regulator of co-ordinated sensory and musculoskeletal actions. The neural tube at the level of rhombomere 1 (hindbrain segment) the caudal portion of the mesencephalic vesicle and the rostral portion of the metencephalic vesicle are the major contributors to cerebellum formation. Development is regulated by the metencephalic-mesencephalic junction (isthmic organizer), which also controls midbrain development. Anatomically in the adult, the cerebellum has a medial domain (vermis) with two lateral subdivisions (cerebellar hemispheres). Histological structure iss a nuclear structure overlaid by a cortical structure, with the deep cerebellar nuclei (DCN) providing the main output centers of the cerebellum. |
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Page Links: Introduction | Some Recent Findings | Development Overview | Gliogenesis and Myelination | Postnatal Neural | References | Glossary | Terms
A recent review of early cerebellum development by Carletti B, Rossi F. Neurogenesis in the cerebellum. Neuroscientist. 2008 Feb;14(1):91-100.
"...review cerebellar neurogenesis and discuss the fate mapping studies with other new information stemming from transplantation experiments, in an effort to link the developmental potential of neural progenitor populations of the cerebellum with their spatio-temporal origin."
Yamada M, Terao M, Terashima T, Fujiyama T, Kawaguchi Y, Nabeshima Y, Hoshino M. Origin of climbing fiber neurons and their developmental dependence on Ptf1a. J Neurosci. 2007 Oct 10;27(41):10924-34.
"Climbing fiber (CF) neurons in the inferior olivary nucleus (ION) extend their axons to Purkinje cells, playing a crucial role in regulating cerebellar function."
Midline section of an early Fetus (week 10) showing the small dorsal cerebellum extensing into the space generated by the pontine brain flexure.
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Mesencephalic/Metencephalic Junction (Boundary) - inductive signaling involving FGF and Wnt proteins
Purkinje cells - secrete Sonic hedgehog (Shh) which regulates cerebellar granule cell precursor proliferation.
Cerebellar granule cell precursors (GCPs) - arise from primary progenitors in the rhombic lip (RL).
Purkinje cell migration - regulated by reelin.
Interneurons - (GABAergic and Glutamatergic) are generated in late embryonic and early postnatal development.
GABAergic interneurons - inside-out sequence of formation, deep nuclei then the granular and molecular layer.
Neuronal Origins
Ventricular Zone - GABAergic neurons, nucleo-olivary projection neurons and Purkinje cells
Rhombic Lip - Glutamatergic deep nuclear neurons
(Data from: Carletti B, Rossi F. Neurogenesis in the cerebellum. Neuroscientist. 2008 Feb;14(1):91-100.)
Three-dimensional magnetic resonance imaging and image-processing algorithms have been used to quantitate between 29-41 weeks volumes of: total brain, cerebral gray matter, unmyelinated white matter, myelinated, and cerebrospinal fluid (grey matter- mainly neuronal cell bodies; white matter- mainly neural processes and glia). A study of 78 premature and mature newborns showed that total brain tissue volume increased linearly over this period at a rate of 22 ml/week. Total grey matter also showed a linear increase in relative intracranial volume of approximately 1.4% or 15 ml/week. The rapid increase in total grey matter is mainly due to a fourfold increase in cortical grey matter. Quantification of extracerebral and intraventricular CSF was found to change only minimally. (text modified from Huppi etal., (1998) Quantitative magnetic resonance imaging of brain development in premature and mature newborns.Ann Neurol 43(2):224-235.) (More? Late Neural Development)
Glial cells have many different types and roles in central and peripheral neural development, though they are typically described as "supportive", and have the same early embryonic origins as neurons. (More? Gliogenesis and Myelination)
Early in neural development a special type of developmental glia, radial glia, provide pathway for developing neuron (neuroblasts) migration out from the proliferating ventricular layer and are involved in the subsequent lamination and columnar organization of the central nervous system.
Types of glia: radial glia, astroglia, oligodendroglia, microglia and Schwann cells.
Neural development continues after birth with substantial growth, death and reorganization occuring during the postnatal period. (More? Postnatal Development - Neural) The references below give a sample of some recent findings and research methods.
Cortex Matures Faster in Youth with Highest IQ (More? NIH - Cortex Matures Faster in Youth with Highest IQ)
Stern CD. Neural induction: old problem, new findings, yet more questions. Development. 2005 May;132(9):2007-21. Review. "During neural induction, the embryonic neural plate is specified and set aside from other parts of the ectoderm. A popular molecular explanation is the 'default model' of neural induction, which proposes that ectodermal cells give rise to neural plate if they receive no signals at all, while BMP activity directs them to become epidermis. However, neural induction now appears to be more complex than once thought, and can no longer be fully explained by the default model alone. This review summarizes neural induction events in different species and highlights some unanswered questions about this important developmental process."
Snook L, Paulson LA, Roy D, Phillips L, Beaulieu C. Diffusion tensor imaging of neurodevelopment in children and young adults. Neuroimage. 2005 Jul 15;26(4):1164-73. "Diffusion tensor magnetic resonance imaging (DTI) was used to study regional changes in the brain's development from childhood (8-12 years, mean 11.1 +/- 1.3, N = 32) to young adulthood (21-27 years, mean 24.4 +/- 1.8, N = 28). ..... These findings suggest a continuation of the brain's microstructural development through adolescence."
Many of the links below are to external resources and require an internet connection.
Links: Earlier References | Journals | Online Textbooks | Search Textbooks | Reviews | Search PubMed | Books | Glossary
Journals: The Cerebellum
"The Cerebellum is an international journal devoted to the science of the cerebellum and its role in ataxia and other medical disorders."
Online Textbooks: Search NLM Online Textbooks- "cerebellum development" : Developmental Biology | The Cell- A molecular Approach | Molecular Biology of the Cell | Endocrinology
Reviews
Carletti B, Rossi F. Neurogenesis in the cerebellum. Neuroscientist. 2008 Feb;14(1):91-100.
Hoshino M. Molecular machinery governing GABAergic neuron specification in the cerebellum. Cerebellum. 2006;5(3):193-8.
Articles
Machold RP, Kittell DJ, Fishell GJ. Antagonism between Notch and bone morphogenetic protein receptor signaling regulates neurogenesis in the cerebellar rhombic lip. Neural Develop. 2007 Feb 23;2:5.
Chizhikov VV, Lindgren AG, Currle DS, Rose MF, Monuki ES, Millen KJ. The roof plate regulates cerebellar cell-type specification and proliferation. Development. 2006 Aug;133(15):2793-804.
Fink AJ, Englund C, Daza RA, Pham D, Lau C, Nivison M, Kowalczyk T, Hevner RF. Development of the deep cerebellar nuclei: transcription factors and cell migration from the rhombic lip. J Neurosci. 2006 Mar 15;26(11):3066-76.
Swanson DJ, Tong Y, Goldowitz D. Disruption of cerebellar granule cell development in the Pax6 mutant, Sey mouse. Brain Res Dev Brain Res. 2005 Dec 7;160(2):176-93.
Engelkamp D, Rashbass P, Seawright A, van Heyningen V. Role of Pax6 in development of the cerebellar system. Development. 1999 Aug;126(16):3585-96.
Note: books are listed for educational and information purposes only and does not suggest a commercial product endorsement.
Molecular and Cellular Approaches to Neural Development
The Embryonic Human Brain: An Atlas Of Developmental Stages, 3rd Edition
Search PubMed
Search Mar2007 "neural development" 9,393 reference articles of which 2,047 were reviews.
Search PubMed: term= neural development | Sonic Hedgehog | Hox | abnormal neural development
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Notes under Development
(notice removed when complete)
Development of the cerebellum occurs relatively late.
The adult cerebellum will contain more neurons that all the other structures of the brain.
We form from a simple plate region of the ectoderm, then fold a simple neural tube, to differentiate into the complex structure of the spinal cord and brain.
Please email Dr Mark Hill if you wish to make a comment about this current project.