title: Postnatal growth of the human pons: a morphometric and immunohistochemical analysis.
abstract: Despite its critical importance to global brain function, the postnatal development of the human pons remains poorly understood. In the present study, we first performed magnetic resonance imaging (MRI)-based morphometric analyses of the postnatal human pons (0-18 years; n = 6-14/timepoint). Pons volume increased 6-fold from birth to 5 years, followed by continued slower growth throughout childhood. The observed growth was primarily due to expansion of the basis pontis. T2-based MRI analysis suggests that this growth is linked to increased myelination, and histological analysis of myelin basic protein in human postmortem specimens confirmed a dramatic increase in myelination during infancy. Analysis of cellular proliferation revealed many Ki67(+) cells during the first 7 months of life, particularly during the first month, where proliferation was increased in the basis relative to tegmentum. The majority of proliferative cells in the postnatal pons expressed the transcription factor Olig2, suggesting an oligodendrocyte lineage. The proportion of proliferating cells that were Olig2(+) was similar through the first 7 months of life and between basis and tegmentum. The number of Ki67(+) cells declined dramatically from birth to 7 months and further decreased by 3 years, with a small number of Ki67(+) cells observed throughout childhood. In addition, two populations of vimentin/nestin-expressing cells were identified: a dorsal group near the ventricular surface, which persists throughout childhood, and a parenchymal population that diminishes by 7 months and was not evident later in childhood. Together, our data reveal remarkable postnatal growth in the ventral pons, particularly during infancy when cells are most proliferative and myelination increases.
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California - San Francisco, San Francisco, CA, 94143; Department of Neurological Surgery, University of California - San Francisco, San Francisco, CA, 94143.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Tate
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lindquist
authors.forename: Thuhien
authors.initials: T
authors.lastname: Nguyen
authors.forename: Nader
authors.initials: N
authors.lastname: Sanai
authors.forename: A James
authors.initials: AJ
authors.lastname: Barkovich
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Huang
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019394:Ki-67 Antigen / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D011149:Pons / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human
keywords: AB_2109815; AB_2304493; AB_2336877; AB_2336878; AB_261856; AB_291466; AB_304558; AB_396287; AB_442102; AB_91107; AB_92396; SciRes_000114; basis; brainstem; development; nif-0000-00217; pediatric; pontine glioma