title: Stereotypical alterations in cortical patterning are associated with maternal illness-induced placental dysfunction.
abstract: We have previously shown in mice that cytokine-mediated damage to the placenta can temporarily limit the flow of nutrients and oxygen to the fetus. The placental vulnerability is pronounced before embryonic day 11, when even mild immune challenge results in fetal loss. As gestation progresses, the placenta becomes increasingly resilient to maternal inflammation, but there is a narrow window in gestation when the placenta is still vulnerable to immune challenge yet resistant enough to allow for fetal survival. This gestational window correlates with early cortical neurogenesis in the fetal brain. Here, we show that maternal illness during this period selectively alters the abundance and laminar positioning of neuronal subtypes influenced by the Tbr1, Satb2, and Ctip2/Fezf2 patterning axis. The disturbances also lead to a laminar imbalance in the proportions of projection neurons and interneurons in the adult and are sufficient to cause changes in social behavior and cognition. These data illustrate how the timing of an illness-related placental vulnerability causes developmental alterations in neuroanatomical systems and behaviors that are relevant to autism spectrum disorders.
authors.affiliation: Stanford University, Institute for Stem Cell Biology and Regenerative Medicine, Stanford, California 94305-5454.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Carpentier
authors.forename: Ursula
authors.initials: U
authors.lastname: Haditsch
authors.forename: Amy E
authors.initials: AE
authors.lastname: Braun
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Cantu
authors.forename: Hyang Mi
authors.initials: HM
authors.lastname: Moon
authors.forename: Robin O
authors.initials: RO
authors.lastname: Price
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Anderson
authors.forename: Vidya
authors.initials: V
authors.lastname: Saravanapandian
authors.forename: Khadija
authors.initials: K
authors.lastname: Ismail
authors.forename: Moises
authors.initials: M
authors.lastname: Rivera
authors.forename: James M
authors.initials: JM
authors.lastname: Weimann
authors.forename: Theo D
authors.initials: TD
authors.lastname: Palmer
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism; D001523:Mental Disorders / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D010920:Placenta / Q000473:pathology* / Q000503:physiopathology; D010922:Placenta Diseases / Q000473:pathology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012919:Social Behavior; D020825:T-Box Domain Proteins; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C511143:Bcl11b protein, mouse; D004268:DNA-Binding Proteins; D036961:Matrix Attachment Region Binding Proteins; D012097:Repressor Proteins; C469541:Satb1 protein, mouse; D020825:T-Box Domain Proteins; C492271:Tbr1 protein, mouse; D025521:Tumor Suppressor Proteins