Congenital hypoplasia of the cerebellum: developmental causes and behavioral consequences

Abstract

Over the last 60 years, the spotlight of research has periodically returned to the cerebellum as new techniques and insights have emerged. Because of its simple homogeneous structure, limited diversity of cell types and characteristic behavioral pathologies, the cerebellum is a natural home for studies of cell specification, patterning, and neuronal migration. However, recent evidence has extended the traditional range of perceived cerebellar function to include modulation of cognitive processes and implicated cerebellar hypoplasia and Purkinje neuron hypo-cellularity with autistic spectrum disorder. In the light of this emerging frontier, we review the key stages and genetic mechanisms behind cerebellum development. In particular, we discuss the role of the midbrain hindbrain isthmic organizer in the development of the cerebellar vermis and the specification and differentiation of Purkinje cells and granule neurons. These developmental processes are then considered in relation to recent insights into selected human developmental cerebellar defects: Joubert syndrome, Dandy–Walker malformation, and pontocerebellar hypoplasia. Finally, we review current research that opens up the possibility of using the mouse as a genetic model to study the role of the cerebellum in cognitive function.

NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development

“…Syndromes such as ataxia are most commonly attributed to deficiencies in this structure (Steinlin 2008;Basson and Wingate 2013). However, more recent human imaging and cerebellar injury studies have broadened the scope of cerebellar function to include aspects of cognition, associative learning, emotional response, and behavior (Timmann et al 2010).…”

The Cerebellum, Sensitive Periods, and Autism

“…This idea is not new: cognitive roles for cerebellum have been discussed since the mid-19th century (reviewed in Steinlin, 2013), with a resurgence of interest in recent years (D'Angelo and Casali, 2012; Koziol et al, 2014; Mariën et al, 2014). Evidence for cerebellar lesions leading to nonmotor deficits has come from adult cases showing subtle cognitive and affective changes (Stoodley et al, 2012), and congenital cerebellar defects, where deficits are much more pronounced (Basson and Wingate, 2013; Steinlin, 2013). …”

A rare case of cerebellar agenesis: a probabilistic Constrained Spherical Deconvolution tractographic study

“…Previous studies paid great attention to the role of cerebellar structural abnormalities in the etiopathogenesis of neuropsychological dysfunctions and a relationship between early development of cognitive functions and extent of vermian lobulation has been reported (Boddaert et al 2003;Basson and Wingate 2013). Some authors also focused on synaptic reorganization, which might establish functional compensation after cerebellar structural damage (Sotelo and Privat 1978).…”