The brainstem is the most evolutionary conserved division of the brain. It develops from the hindbrain and midbrain regions of the neural tube and forms neural networks that regulate vital functions of the body. One of the most critical roles is to generate respiratory rhythm for the regulation of oxygen, carbon dioxide and pH levels. This is achieved by pacemaker neurons and neural networks in the medulla oblongata, controlled by different modulatory systems. The mechanisms whereby the respiratory rhythm is generated and regulated are not fully understood and have only recently started to be unveiled. This thesis describes the importance of two different gene products, KCC2 and Vangl2, for proper development of the brainstem. We show that, while these genes act in separate phases of development, they share the common feature of regulating the integrity of the neuronal cytoskeleton necessary for maturation of the brainstem. KCC2 is a neuronal K+/Cl-cotransporter that is responsible for the developmental shift in the postsynaptic response to GABA. A fundamental premise for this thesis is that we found KCC2 protein expression in the hindbrain region of mice already at embryonic day 9.5, although its ion transport activity does not become functional until late fetal age. We show that the depolarizing effect of GABA elicits increased activity of fetal respiration-related neurons. In addition, the developmental GABA shift is associated with plasma membrane targeting of KCC2 in respiration-related regions of rats around birth. Overexpression of KCC2 in the mouse neural tube resulted in altered neuronal differentiation and neural crest migration. These effects were independent of the ion transport function of KCC2 and were shown to rely on a structural interaction with the cytoskeleton-associated protein 4.1N. Thus, transport-inactive KCC2 may regulate neuronal differentiation and migration during early development. We assessed the early importance of KCC2 further in mice knockout for this gene, which die at birth from ...